1. Field of the Invention
This invention relates to flunisolide hemihydrate, treatment of inflammatory or infectious diseases of the respiratory tract using it and therapeutically useful preparations containing it.
2. Prior Art
Flunisolide is the common name of a known compound, 6.alpha.-fluoro-11.beta.,21-dihydroxy-16.alpha.,17.alpha.-isopropylidenedi oxypregna-1,4-diene-3,20-dione. Its structural formula is, thus, ##STR1## Procedures for making compounds of this type are described in U.S. Pat. No. 3,126,375 to Ringold et al. Flunisolide has anti-inflammatory and anti-pyretic activity and has had primary utility in the treatment of topical inflamed conditions. The compound is previously unknown to be polymorphic but it has now been discovered that there are several polymorphic forms. In addition, the hemihydrate of the formula ##STR2## is particularly stable in the presence of aerosol propellants so that it may be readily formulated to form an aerosol which is particularly valuable in the treatment of respiratory diseases such as bronchial asthma, allergic rhinitis, and others which respond to treatment by suitable steroids.
It is generally known in the art that certain specific steroids may be used for the treatment of asthma, for example, hydrocortisone and prednisolone have been used as an aerosol suspension. (See for example J. Allergy, 29 (3), 214-221, 1958.) Other steroids which have been used in various formulations include dexamethasone phosphate (See U.S. Pat. No. 3,282,791 to Macek; J. Allergy, 34 (2), 119-126, March-April, 1963), betamethasone 17-valerate (see JAMA, 231 (4), 406-407, Jan. 27, 1975) and triamcinolone acetonide (see J. Allergy, 33 (1), 1-5, January-February, 1962 and American Review of Respiratory Disease, 109, 538-543, 1974). It is also known that beclomethasone dipropionate (9.alpha.-chloro-16.alpha.-methyl-prednisolone-17.alpha.,21-dipropionate) along with certain other steroids such as fluocinolone acetonide (6.alpha.,9.alpha.-difluoro-11.beta.,21-dihydroxy-16.alpha.,17.alpha.-isop ropylidenedioxy-pregna-1,4-diene-3,20-dione) may be used in aerosol formulations as taught in German Offenlegungschrift No. 2,320,111. However, that patent teaches that if these steroids are placed in the aerosol formulation without previous treatment the particles tend to increase in size and deposit on the sides of the can or along the throat of the release tube and may ultimately plug the tube or change the concentration of the aerosol released. Thus, that patent teaches that if the steroid is first solvated according to the process described, the solvated steroid does not tend to increase in particle size nor drop out of the dispersion in the aerosol formulation.
Surprisingly, it has now been found that a flunisolide hemihydrate is stable in aerosol formulations which use suitable fluorinated and chlorinated hydrocarbon propellants. This heretofore unknown compound, because of these properties, is useful in the treatment of bronchial asthma, allergic rhinitis or other respiratory ailments.